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IntroductionThe elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction.Methods and analysisThis will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20–49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass indexEthics and disseminationThe study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal.Trial registration numberjRCTb030200391.

There has recently been growing interest worldwide in biological therapies such as platelet-rich plasma injection for the treatment of knee osteoarthritis. However, predicting the effectiveness of platelet-rich plasma therapy remains uncertain. Therefore, this retrospective cohort study was performed to assess a range of predictors for the effectiveness of platelet-rich plasma therapy in treating knee osteoarthritis. The study included 517 consecutive patients who underwent three injections of leucocyte-poor platelet-rich plasma therapy from 2016 to 2019 at a single institution. The treatment outcomes, including patient-oriented outcomes (visual analogue scale score and Knee Injury and Osteoarthritis Outcome Score), were analyzed and compared according to the severity of knee osteoarthritis based on Kellgren–Lawrence (KL) grading using standing plain radiographs. Fisher’s exact test, univariate regression, and multivariate regression were used for data analysis. Patient-oriented outcomes were significantly improved 6 and 12 months after platelet-rich plasma therapy. The overall responder rate in patients who met the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) responder criteria was 62.1%. The responder rate was significantly lower in patients with severe knee osteoarthritis (KL4, 50.9%) than in those with mild (KL2, 75.2%) and moderate (KL3, 66.5%) knee osteoarthritis. The multivariate logistic regression analysis revealed that deterioration of the knee osteoarthritis grade (increased KL grade) was a significant predictor of a worse clinical outcome (odds ratio, 0.58, 95% confidence interval, 0.45–0.75, p &lt, 0.001). The relative risk for non-responders in severe (KL4) KOA was 2.1 (95% CI, 1.5–3.0) at 6 months and 2.3 (1.6–3.2) at 12 months compared with mild-to-moderate (KL2-3) KOA. The efficacy of platelet-rich plasma therapy was not affected by age, sex, body weight, or platelet count. This study revealed that the effectiveness of platelet-rich plasma therapy for the treatment of knee osteoarthritis is approximately 60% and that the effectiveness depends on the severity of knee osteoarthritis. This observation is useful not only for physicians but also for patients with knee osteoarthritis.

Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have reported an association between polymorphisms of the collagen XII gene COL12A1 and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. Therefore, we hypothesized that collagen XII deficiency may cause ACL injury. To elucidate the influence of collagen XII deficiency on ACL, we analyzed a mouse model deficient for Col12a1. Four- to 19-week-old male Col12a1-/- and wild-type control mice were used for gait analysis, histological and immunofluorescent analysis of collagen XII, and real-time RT-PCR evaluation of Col12a1 mRNA expression. The Col12a1-/- mice showed an abnormal gait with an approximately 2.7-fold increase in step angle, suggesting altered step alignment. Col12a1-/- mice displayed 20–60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities in knee ligaments were found in wild-type mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury.

Introduction: Knee osteoarthritis (KOA), the most common form of osteoarthritis (OA) is a considerable health concern worldwide. Platelet-rich plasma (PRP) is a common therapeutic option for KOA. Different types of PRPs have varying efficacies. However, a comparative analysis of the qualities of these PRPs is lacking. Methods: Two types of PRPs, including autologous protein solution (APS), and leukocyte-poor PRP (LP-PRP) along with whole blood (WB) and platelet-poor plasma (PPP) were characterized for platelet content, leukocyte content, and composition in 10 healthy volunteers (HV) (the controlled laboratory study) and 16 KOA patients (a retrospective observational study). Additionally, the levels of the platelet-derived growth factor (PDGF)-BB, and different cytokines were estimated in HV. Results: In HV, the concentrations of platelets and leukocytes, levels of different cytokines, including interleukin 1 receptor antagonist (IL-1Ra), soluble TNF receptor type II (sTNF-RII), and IL-1β, and the ratio of IL-1Ra/IL-1β were significantly higher in APS, whereas the PDGF-BB was higher in LP-PRP than APS. In KOA patients, a higher concentration of platelets was observed in LP-PRP, and a higher concentration of leukocytes was observed in APS than LP-PRP. Following the PAW classification system, LP-PRP was classified as P2-B type in HV (51.3 × 104/μl) and KOA (53.4 × 104/μl), whereas APS was classified as P3-A type in HV (110.1 × 104/μl) and P2-A type in KOA (29.0 × 104/μl). In a retrospective observational study, the KOA patients who underwent APS injection had a higher incidence of arthralgia, and this arthralgia lasted for a longer time than LP-PRP injection in the same individual. Discussion: The quality of the two PRPs differed distinctively depending on their preparation methods, which might affect their clinical efficacies and adverse events. Therefore, the characterization of these parameters should be prioritized while choosing PRP.